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Boldt inquiry concludes: False findings in at least 10 studies, but no harm to patients

Ludwigshafen Hospital, via Wikimedia http://bit.ly/Qnt9wS

It has been a while since we heard about Joachim Boldt, the German anesthesiologist whose 90-odd retractions briefly put him at the top of the heap until Yoshitaka Fujii kicked him off earlier this year.

Now, Boldt’s former institution, the Klinikum Ludwigshafen, has released a report on its investigation into the disgraced critical care expert, and the results aren’t pretty. Here’s a press release about the report, in its entirety:

09.08.2012

After an investigation lasting approximately 18 months and involving the examination of 91 scientific articles, the independent committee convened by Ludwigshafen Hospital to investigate allegations of scientific fraud brought against Dr. Joachim Boldt has published its final report. As a result of the allegations against him, Dr Boldt left the Hospital in November 2010. Following his departure an Investigation Committee, consisting of six investigators, was convened to examine allegations of scientific fraud and to investigate potential infringements of patients’ rights and/or instances of patient harm. The Committee’s report concludes that no patients were harmed as a result of the former consultant’s professional and research conduct. However, the Committee’s report also establishes several instances of misconduct on the part of Dr Boldt.

The Committee’s findings are based on the examination of 91 articles authored or co-authored by Dr Boldt, and published between 1999 and 2011. Examination of these articles revealed that study files were either missing or incomplete for the large majority of the studies concerned, suggesting that Dr Boldt failed in his duty as principal investigator to comply with current regulations pertaining to the retention of study data. None of the studies examined had received an ethical opinion from the Rhineland-Palatinate Medical Association (Landesärztekammer Rheinland-Pfalz). In the majority of these cases, the principal investigator had failed to register planned research projects with the Rhineland-Palatinate Medical Association, and the relevant office at Ludwigshafen Hospital. Many cases revealed no record of formal consent by study participants or indeed evidence that study participants had been provided with sufficient information prior to enrolment.

The Committee reports that in a large number of the studies investigated, the conduct of research failed to meet required standards. False data were published in at least 10 of the 91 articles examined, including, for instance, data on patient numbers/ study groups as well as data on the timing of measurements.

The Committee’s findings include clear evidence of procedural irregularities and research misconduct on the part of Dr Joachim Boldt.

However, the Committee was also able to report that no patients had been physically harmed in the process. The Committee was able to establish the identities of 455 patients whose data had contributed to Dr Boldt’s research studies. These patients’ medical records were examined for possible adverse events and serious adverse events as defined by current GCP (Good Clinical Practice) classification criteria.

The majority of the patients identified in this manner were older patients with multiple comorbidities. Administration of the study drug, which at the time was in routine use within Ludwigshafen Hospital and other hospitals, was shown to be associated with only one such event.

Fortunately, this episode was resolved without the patient suffering any lasting harm. A further patient was successfully treated following a serious adverse event and suffered no lasting harm. A possible causal relationship with the study drug, however, could not be excluded. Both patients concerned were duly notified by the appropriate clinical directorate.

“We strongly disapprove of the conduct of Dr Boldt and distance ourselves from his actions and regret that these incidents occurred,” said Ludwigshafen Hospital’s Managing Director, Dr. Joachim Stumpp. “The independent inquiry’s conclusion, that there is no evidence of any study-related adverse effects, has come as a great relief,” The Hospital has also passed the Committee’s report on to the appropriate public prosecutor’s office.

Shortly after the allegations against the former consultant anaesthetist were made public, Ludwigshafen Hospital responded by tightening procedural requirements relating to the conduct of clinical studies. Of particular significance was the decision to create a Scientific Steering Committee (Gremium der Wissenschaft, or GW). The GW’s remit will be to monitor all clinical studies conducted within the Hospital, thus ensuring that appropriate quality standards are maintained, and that participating study doctors are able to access detailed guidance and support.

“The Hospital’s response to this unfortunate incident has been to review internal processes and procedures,” said Dr. Stumpp. “We have done everything within our power to ensure that Ludwigshafen Hospital can meet the highest possible standards in terms of the statutory requirements pertaining to the conduct of research studies, including those relating to patients’ rights.”

The drug the release refers to most likely is hydroxyethyl starch, which is used as fluid support.

So, to summarize: Boldt’s initial retraction from Anesthesia & Analgesia, the one that set the wheels of the investigation in motion — thanks to the dogged efforts of the journal’s editor, Steven Shafer — involved bogus data. But that wasn’t the only instance of fraud, even if the vast bulk of his deception had to do with lack of ethics approval, lack of proper informed consent and other (admittedly serious) infractions.

15 thoughts on “Boldt inquiry concludes: False findings in at least 10 studies, but no harm to patients”

The report mentions that “Dr. Bolt failed in his duty as principal investigator to comply with current regulations pertaining to the retention of study data.” While I understand that it is advisable to keep the data for future use, I have never heard of any regulations about this…

“Now, Boldt’s former institution, the Klinikum Ludwigshafen, has released a report on its investigation into the disgraced critical care expert, and the results aren’t pretty.”

At least these people came up with a report without removing names. In Canada, funding agencies like NSERC may release reports to journalists under Access to Information Act but they make sure that the documents are heavily censored and all names are blackened out: http://www.nature.com/nature/journal/v477/n7366/full/477509b.html

You can see that the name of the researcher “still getting federal funds despite misconduct finding” is blackened out. The institution’s name is also blackened out. In this particular case, we were lucky because my letter of complaint to NSERC was also published in the same article. So, we were sure that the name of scientist was Reginald W Smith, and the name of his institution involved in misconduct was Queen’s University, Kingston, Ontario (CANADA).

However, the Committee was also able to report that no patients had been physically harmed in the process.

but then only two paragraphs later state:

Fortunately, this episode was resolved without the patient suffering any lasting harm. A further patient was successfully treated following a serious adverse event and suffered no lasting harm.

On the one hand the “Committee ” is stating no one was harmed but on the other hand they are saying at least two patients were harmed due to the “study drug” but fortunately recovered after a period of time.

Please tell me which statement is accurate. Either no one was hurt or at least two were hurt by being injected with an experimental “study drug”.

Here is the full wording:
The majority of the patients identified in this manner were older patients with multiple comorbidities. Administration of the study drug, which at the time was in routine use within Ludwigshafen Hospital and other hospitals, was shown to be associated with only one such event. Fortunately, this episode was resolved without the patient suffering any lasting harm. A further patient was successfully treated following a serious adverse event and suffered no lasting harm. A possible causal relationship with the study drug, however, could not be excluded.

Rough translation:
Most of the patients in the study had other things wrong with them that could have caused bad health problems to occur during the study period. (A co-morbidity is another disease that the patient has. It might be either entirely independent of the disease of interest or related in some way to the disease of interest.) One patient did develop a problem during the course of the research and it seemed to be associated with the study drug, but that means the health problem and the administration of the study drug were associated, not that the study drug necessarily was the direct cause. Correlation is not necessarily causation. The health problem could have been just chance. One other patient developed a bad problem during the study. In that case, there was no obvious association between the health problem and the study drug. However, the study drug might have been the cause. It could not be absolutely ruled out as the cause.

So, putting the most positive construction on things, the committee concluded there was no concrete proof that harm came to the patients in the study. There were two cases of bad health problems, but neither case was obviously and definitely caused by the study drug and luckily both patients recovered. No (permanent, unequivocal) harm, no foul, I guess.

Administration of the study drug, which at the time was in routine use within Ludwigshafen Hospital and other hospitals,was shown to be associated with only one such event.

Fortunately, this episode was resolved without the patient suffering any lasting harm.

If you delete all the weasel words and obfuscation I can only conclude that at least one patient was harmed by being administered the experimental “study drug” though it is being dismissed by the committee because it was only “short term harm” and the patient recovered.

A further patient was successfully treated following a serious adverse event and suffered no lasting harm. A possible causal relationship with the study drug, however, could not be excluded.

As for the second patient, while they could not conclude that the experimental drug was the cause of his/her problems neither could they rule it out. In other words, they are just guessing when they say it didn’t cause patient two’s problems. (And oops, there is that “it didn’t cause any lasting , harm phrase again when the committee clearly stated nobody was harmed by the administration of the experimental drug.)

It is very disingenuous for the independent committee to unequivocally state that out of 455 patients no one was hurt by the use of this experimental “study drug” then to go on to imply that one, if not two, patients may have been hurt by the drug.

Oh, and it also stated that a “majority of the patients” were elderly and had multiple comorbidities it didn’t state that “all” of them were elderly with multiple comorbidities. So to be fair neither you nor I can state whether or not the two patients that had adverse reactions had any underlying health problems at all or were “elderly”. The two patients in question could easily have been healthy twenty somethings or 70 year old elderly patients with multiple health issues. We will never know due to the strict German privacy laws and the fact that the good doctor’s research papers are incomplete.

If it were not for the privacy laws, we should be able to track down the specifics on the two patients who suffered “adverse events”. The committee was able to see the identities and medical records for the two instances of possible harm. In my reading of the committee’s words, patient #1’s event was only “associated with” administration of the study drug, not necessarily caused by it. Correlation is not causation. And more than one data point would be needed to demonstrate a cause-and-effect relationship.

But I agree with you that the committee is taking great liberties with language in asserting that no patients were harmed when in fact there is a slight chance that two patients were harmed in the short term. And naturally the general public is not comforted by the idea that short-term harm is described as “no harm” by the hospital committee, as if only permanent harm is worth counting.

There is actually a difference between the German ( I suppose original ) and the English (supposedly translated) version of the press release, the German version does not state that no patient was harmed, it says ” … konnte die Kommission erfreulicherweise in der Frage nach möglichen Gesundheitsschädigungen der Patienten Entwarnung geben.”

The commission could give “Entwarnung” concerning the question of possible health damage of patients.
“Entwarnung” literally translates as “all-clear” or “de-warning”, but that does not seem to quite catch the twist of the meaning in German in this context. Roughly, in this context one could read it as “Luckily the commission found no evidence of (permanent) damage to the health of the patients”. Later on then, the non-permanent damage of the two patients mentioned is then elaborated on. I am afraid a true 1:1 translation in this case is beyond my capabilities.

It is well possible that the here critizized “no harm to the patients” is more due to problems in translation than the meaning that was intended.

Now, if you would say that you should pay more attention on the translation in such an important issue, I wouldn’t argue with that.

The title of this piece (“Boldt inquiry concludes: False findings in at least 10 studies, but no harm to patients”) seems somewhat disingenuous to me. While Ludwigshafen Hospital’s Managing Director has concluded that “there is no evidence of any study-related adverse effects,” this does not prove that no harm to patients occurred.

First, one would expect the hospital where the infractions occurred to be busy covering its legal liability with a cloud of self-serving words. Second, harm to patients can arise outside the context of a study. Boldt encouraged use of HES long after evidence had accumulated that it could be harmful, and he did this by fabricating and falsifying data. Hence, he should be accountable for any harm to patients who received HES after the weight of other evidence should have argued against its use.

Exactly. How many (thousands of) patients have died or have received renal replacement therapy because of his fabricated data? And it continues – the notion of harm associated with colloids still hasn’t spread everywhere it should.

Saying that it is a matter of translating the press release from one language to another, in this case German to English, is a valid concern. However, consider the following.

“We strongly disapprove of the conduct of Dr Boldt and distance ourselves from his actions and regret that these incidents occurred,” said Ludwigshafen Hospital’s Managing Director, Dr. Joachim Stumpp. “The independent inquiry’s conclusion, that there is no evidence of any study-related adverse effects, has come as a great relief,” The Hospital has also passed the Committee’s report on to the appropriate public prosecutor’s office.

“We distance ourselves emphatically from the practices of Dr. Boldt and very sorry for the incident. For us it is a great relief that the independent commission concluded that except for two cases, no study-related disadvantages were detectable.” Says Dr. Joachim Stumpp, CEO of the hospital in Ludwigshafen. The hospital has submitted the final report to the public prosecutor. (Emphasis added)

Now admittedly while Google Translate sometimes gives results that could be called unique, I find it better than most of the other offerings. In light of that, could someone please be so kind as to explain why the short phrase, “except for two cases” seems to be omitted from CEO Dr. Stumpp’s quote in the English version?

No wonder the English press release is so confusing. The translator left out some rather important phrases when translating the press release to English.